Search Results (606)

Noncommunicable diseases (NCDs) like diabetes and cancer drive demand for therapeutic functional foods. This study developed freeze-dried fermented camel milk (FCM) with Ajwa date pulp (ADP), evaluating its physical and functional properties, probiotic survival, and potential benefits for diabetes and cancer. To achieve this target, six FCM formulations were prepared using ABT-5 starter culture (containing Lactobacillus acidophilus, Bifidobacterium bifidum, and Streptococcus thermophilus) with or without Lacticaseibacillus rhamnosus B-1937 and ADP (12% or 15%). The samples were freeze-dried, and their functional properties, such as water activity, dispersibility, water absorption capacity, water absorption index, water solubility index, insolubility index, and sedimentation, were assessed. Reconstitution properties such as density, flowability, air content, porosity, loose bulk density, packed bulk density, particle density, carrier index, Hausner ratio, porosity, and density were examined. In addition, color and probiotic survivability under simulated gastrointestinal conditions were analyzed. Also, antidiabetic potential was assessed via α-amylase and α-glucosidase inhibition assays, while cytotoxicity was evaluated using the MTT assay on Caco-2 cells. The results show that ADP supplementation significantly improved dispersibility (up to 72.73% in FCM15D+L). These improvements are attributed to changes in particle size distribution and increased carbohydrate and mineral content, which facilitate powder rehydration and reduce clumping. All FCM variants demonstrated low water activity (0.196–0.226), indicating good potential for shelf stability. The reconstitution properties revealed that FCM powders with ADP had higher bulk and packed densities but lower particle density and porosity than controls. Including ADP reduced interstitial air and increased occluded air within the powders, which may minimize oxidation risks and improve packaging efficiency. ADP incorporation resulted in a significant decrease in lightness (L*) and increases in redness (a*) and yellowness (b*), with greater pigment and phenolic content at higher ADP levels. These changes reflect the natural colorants and browning reactions associated with ADP, leading to a more intense and visually distinct product. Probiotic survivability was higher in ADP-fortified samples, with L. acidophilus and B. bifidum showing resilience in intestinal conditions. The FCM15D+L formulation exhibited potent antidiabetic effects, with IC₅₀ values of 111.43 μg mL⁻¹ for α-amylase and 77.21 μg mL⁻¹ for α-glucosidase activities, though lower than control FCM (8.37 and 10.74 μg mL⁻¹, respectively). Cytotoxicity against Caco-2 cells was most potent in non-ADP samples (IC₅₀: 82.22 μg mL⁻¹ for FCM), suggesting ADP and L. rhamnosus may reduce antiproliferative effects due to proteolytic activity. In conclusion, the study demonstrates that ADP-enriched FCM is a promising functional food with enhanced probiotic viability, antidiabetic potential, and desirable physical properties. This work highlights the potential of camel milk and date synergies in combating some NCDs in vitro, suggesting potential for functional food application. Full article

Benzothiazole derivatives have emerged as being highly significant in drug discovery due to their versatile biological activities and structural adaptability. Incorporating nitrogen and sulfur, this fused heterocyclic scaffold exhibits wide-ranging pharmacological properties, including anticancer, antimicrobial, anti-inflammatory, antidiabetic, neuroprotective, and diagnostic applications. A diverse set of clinically approved and investigational compounds, such as flutemetamol for Alzheimer’s diagnosis, riluzole for ALS, and quizartinib for AML, illustrates the scaffold’s therapeutic potential in varied applications. These agents act via mechanisms such as enzyme inhibition, receptor modulation, and amyloid imaging, demonstrating the scaffold’s high binding affinity and target specificity. Advances in synthetic strategies and our understanding of structure–activity relationships (SARs) continue to drive the development of novel benzothiazole-based therapeutics with improved potency, selectivity, and safety profiles. We also emphasize recent in vitro and in vivo studies, including drug candidates in clinical trials, to provide a comprehensive perspective on the therapeutic potential of benzothiazole-based compounds in modern drug discovery. This review brings together recent progress to help guide the development of new benzothiazole-based compounds for future therapeutic applications. Full article

The marine seaweed Undaria pinnatifida belongs to the large group of brown macroalgae (Ochrophyta) and is valued both as a nutritious food and a source of pharmaceutical compounds. It has been widely consumed in East Asia as part of the traditional diet and is generally regarded as a “healthy longevity food.” Consequently, it represents one of the most promising natural sources of biomedicinal and bioactive products. This review aims to synthesize current scientific evidence on the pharmacologically active compounds of U. pinnatifida, emphasizing their mechanisms of action and therapeutic potential in neurodegenerative and chronic diseases. This narrative review is based on a comprehensive literature search of peer-reviewed articles from scientific databases, focusing on studies addressing the pharmacological properties of U. pinnatifida and its major bioactive constituents. Recent research highlights that compounds such as fucoxanthin (a carotenoid), fucosterol (a sterol), fucoidan (a polysaccharide), alginate, and dietary fiber found in U. pinnatifida possess significant potential for developing treatments for conditions including goitre, urinary diseases, scrofula, dropsy, stomach ailments, and hemorrhoids. Moreover, these compounds exhibit remarkable pharmacological properties, including immunomodulation, antitumor, antiviral, antioxidant, antidiabetic, anti-inflammatory, anticoagulant, antithrombotic, and antibacterial activities, all with low toxicity and minimal side effects. Additionally, U. pinnatifida shows promise in the treatment or prevention of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as neuropsychiatric conditions like depression, supported by its antioxidant effects against oxidative stress and neuroprotective activities. Numerous in vitro and in vivo studies have confirmed that U. pinnatifida polysaccharides (UPPs), particularly fucoidans, exhibit significant biological activities. Thus, accumulating evidence positions UPPs as promising therapeutic agents for a variety of diseases. Full article

Pasteurella multocida (Pm) is a zoonotic pathogen that poses a significant threat to animal health and causes substantial economic losses, further aggravated by rising tetracycline resistance. To restore the efficacy of tetracyclines to Pm, we evaluated the synergistic antibacterial activity of doxycycline combined with metformin, an FDA-approved antidiabetic agent. Among several non-antibiotic adjuvant candidates, metformin exhibited the most potent in vitro synergy with doxycycline, especially against capsular serogroup A strain (PmA). The combination demonstrated minimal cytotoxicity and hemolysis in both mammalian and avian cells and effectively inhibited resistance development under doxycycline pressure. At 50 mg/kg each, the combination of metformin and doxycycline significantly reduced mortality in mice and ducks acutely infected with PmA (from 100% to 60%), decreased pulmonary bacterial burdens, and alleviated tissue inflammation and damage. Mechanistic validation confirmed that metformin enhances membrane permeability in Pm without compromising membrane integrity, dissipates membrane potential, increases intracellular doxycycline accumulation, and downregulates the transcription of the tetracycline efflux gene tet(B). Morphological analyses further revealed pronounced membrane deformation and possible leakage of intracellular contents. These findings highlight metformin as a potent, low-toxicity tetracycline adjuvant with cross-species efficacy, offering a promising therapeutic approach for managing tetracycline-resistant Pm infections. Full article

This study presents the synthesis and antidiabetic and hematopoietic activity of ionic compounds based on 2-(diphenylmethoxy)-N,N-dimethylethanamine (diphenhydramine). Synthesis is carried out under ultrasonic (US) and microwave (MW) irradiation as well as using a conventional method (thermal activation). The synthesized ionic compounds have been tested for antidiabetic effect according to the inhibitory action against α-glucosidase and α-amylase (in vitro). All the synthesized derivatives of diphenhydramine showed higher inhibitory activity against α-glucosidase than commercially available diphenhydramine hydrochloride. Moreover, two of them, 1m (66.9%) and 1k (64.2%), had a greater inhibitory activity than the reference drug acarbose (51.8%). The hematopoietic activity was studied in albino laboratory female rats (in vivo). The compounds 1b, 1f, and 1k can restore immune blood cells (hematopoietic activity), equal to or exceeding that of the commercially available diphenhydramine hydrochloride and control (methyluracil). Full article

Diabetes mellitus is a chronic metabolic disease that has a significant impact on public health and is becoming more and more common worldwide. Although effective, conventional therapies are often limited by high cost, adverse effects, and issues with patient compliance. As a result, there is growing interest in complementary and alternative therapies. Medicinal plants have played an essential role in diabetes treatment, especially in regions such as Romania, where biodiversity is high and traditional knowledge is well preserved. The pathophysiology, risk factors, and worldwide burden of diabetes are examined in this review, with an emphasis on the traditional use of medicinal plants for glycemic control. A total of 47 plant species were identified based on ethnopharmacological records and recent biomedical research, including both native flora and widely cultivated species. The bioactive compounds identified, such as flavonoids, triterpenic saponins, polyphenols, and alkaloids, have hypoglycemic effects through diverse mechanisms, including β-cell regeneration, insulin-mimetic action, inhibition of α-glucosidase and α-amylase, and oxidative stress reduction. A systematic literature search was conducted, including in vitro, in vivo, and clinical studies relevant to antidiabetic activity. Among the species reviewed, Urtica dioica, Silybum marianum, and Momordica charantia exhibited the most promising antidiabetic activity based on both preclinical and clinical evidence. Despite promising preclinical results, clinical evidence remains limited, and variability in phytochemical content poses challenges to reproducibility. This review highlights the potential of Romanian medicinal flora as a source of adjunctive therapies in diabetes care and underscores the need for standardization and clinical validation. Full article

The plant Synsepalum dulcificum is notable for its considerable edible and medicinal value, with a longstanding history as a folk remedy for diabetes. Its chemical constituents are rich and structurally diverse. However, there is limited information regarding the metabolic basis of these characteristics, and the biological activities and mechanisms underlying its blood glucose-lowering effects remain incompletely understood. In this study, we conducted a widely targeted metabolomics analysis of the stems, leaves, and fruits of S. dulcificum using UPLC-ESI-MS/MS to compare the differences in metabolite profiles among these three tissue types. Our analysis identified a total of 2544 secondary metabolites, primarily consisting of flavonoids and triterpenes, categorized into thirteen distinct compound classes. We selected differential metabolites through multivariate statistical analysis, revealing significant differences among the metabolite profiles of the three tissue types, with flavonoids being the most abundant compounds. Furthermore, we investigated the anti-diabetic mechanisms and potential pharmacological components of S. dulcificum utilizing network pharmacology and molecular docking techniques. Finally, the α-glucosidase inhibitory activity of the potential active components was evaluated using in vitro experiments. These findings establish a foundation for the future application of S. dulcificum in the prevention and treatment of diabetes. Full article

The study focused on the distribution of polyphenolic compounds, iridoids, organic acids, and sugars, as well as in vitro antioxidant, anti-inflammatory, antidiabetic, antiproliferation, and antibacterial potential, and physicochemical properties between the skin and flesh of 10 haskap berry (Lonicera caerulea var. kamtschatica Sevast.) cultivars. It was found that the content of individual bioactive compounds significantly depended on the fruit cultivar and the analyzed morphological part. Anthocyanins, kaempferol derivatives and iridoids dominated in the skin, which significantly correlated with most of the analyzed health-promoting properties. In turn, the flesh showed a higher content of quercetin derivatives, sugars and organic acids. No differences were found in the content of phenolic acids, flavan-3-ols and antibacterial activity. The most beneficial properties were shown for the cultivar (cv.) ‘Honeybee’. The study suggests that haskap fruit skin is a valuable raw material for use in the pharmaceutical and food industries. Full article

Background/Objectives: Mesoporous silica materials, particularly KIT-6, offer promising features, such as large surface area, tunable pore structures, and biocompatibility, making them ideal candidates for advanced drug delivery systems. The aims of this study were to develop and evaluate an innovative modified-release platform for metformin hydrochloride (MTF), using KIT-6 mesoporous silica as a matrix, to enhance oral antidiabetic therapy. Methods: KIT-6 was synthesized using an ultrasound-assisted sol-gel method and subsequently loaded with MTF via adsorption from alkaline aqueous solutions at two concentrations (1 and 3 mg/mL). The structural and morphological characteristics of the matrices—before and after drug loading—were assessed using SEM-EDX, TEM, and nitrogen adsorption–desorption isotherms (the BET method). In vitro drug release profiles were recorded in simulated gastric and intestinal fluids over 12 h. Kinetic modeling was performed using seven classical models, and a multifractal theoretical framework was used to further interpret the complex release behavior. Results: The loading efficiency increased with increasing drug concentration but nonlinearly, reaching 56.43 mg/g for 1 mg/mL and 131.69 mg/g for 3 mg/mL. BET analysis confirmed significant reductions in the surface area and pore volume upon MTF incorporation. In vitro dissolution showed a biphasic release: a fast initial phase in an acidic medium followed by sustained release at a neutral pH. The Korsmeyer–Peppas and Weibull models best described the release profiles, indicating a predominantly diffusion-controlled mechanism. The multifractal model supported the experimental findings, capturing nonlinear dynamics, memory effects, and soliton-like transport behavior across resolution scales. Conclusions: The study confirms the potential of KIT-6 as a reliable and efficient carrier for the modified oral delivery of metformin. The combination of experimental and multifractal modeling provides a deeper understanding of drug release mechanisms in mesoporous systems and offers a predictive tool for future drug delivery design. This integrated approach can be extended to other active pharmaceutical ingredients with complex release requirements. Full article

Background: Probiotics have recently emerged as promising agents in the prevention and treatment of various human diseases. This study investigates the therapeutic potential of Weizmannia coagulans SA9 in the management of type 2 diabetes mellitus (T2DM). Methods: The in vitro antidiabetic activity of W. coagulans SA9 was primarily assessed via its α-glucosidase inhibitory capacity, complemented by metabolomic profiling to identify putative bioactive metabolites. The antidiabetic efficacy was further evaluated in a db/db mouse model, focusing on glucose tolerance, inflammatory biomarkers, and gut microbiota composition. Results: W. coagulans SA9 showed significant inhibitory effects on α-glucosidase and α-amylase, and DNJ and other active substances were detected in its culture supernatant. After 6 weeks of continuous administration, the fasting blood glucose level, glucose tolerance, and inflammation indexes of mice were significantly improved. Beneficial changes in the structure of the intestinal flora occurred after the probiotic intervention, as evidenced by a significant decrease in harmful bacteria (e.g., Aerococcus urinaeequi) and a significant enrichment of beneficial bacteria (e.g., Limosilactobacillus reuteri). Conclusions: W. coagulans SA9 exerts robust antidiabetic effects and holds promise as a novel strategy for the prevention and management of T2DM. Full article

The Moroccan coastline has been the focus of attention for researchers studying the national algal flora, with the aim of preserving these invaluable natural resources. Since the year 2000, these resources have stimulated great interest in the creation of new drugs, as well as their integration into food supplements and foods. Therefore, this study aims to explore the phytochemistry of a series of extracts derived from Caulerpa prolifera. To ensure better extraction of the various metabolites present, two extraction methods, namely maceration and the Soxhlet method, were employed using solvents of varying polarity (hexane, ethyl acetate, methanol, and water). The chemical composition of the extracts was analyzed using GC-MS for fatty acids and HPLC-DAD for phenolic compounds. Antioxidant activity was evaluated using DPPH and β-carotene bleaching assays, while antidiabetic potential was assessed by in vitro inhibition of α-amylase and α-glucosidase. In addition, Molecular docking models were employed to assess the interaction between the bioactive molecules and the human pancreatic α-amylase and α-glucosidase enzymes. Vanillin, p-coumaric acid, sinapic acid, 7,3′,4′-flavon-3-ol, and kaempferol were the most abundant phenolic compounds. Anti-diabetic and antioxidant effects were highly significant. Full article

Aim: Myricetin, a natural bioflavonoid, is reported as an anti-diabetic agent since it possesses the ability to inhibit α-glucosidase activity, stimulate insulin action and secretion, manage ROS, and prevent diabetes complications. Myricetin was identified as a new insulin secretagogue that enhances glucose-stimulated insulin secretion and seems like a better antidiabetic drug candidate. Here, we explored the insulinotropic mechanism(s) of myricetin in vitro in mice islets and in silico. Methods: Size-matched pancreatic islets were divided into groups and incubated in the presence or absence of myricetin and agonists/antagonists of major insulin signaling pathways. The secreted insulin was measured by ELISA. Molecular docking studies were performed with the key player of insulin secretory pathways. Results: Myricetin dose-dependently enhanced insulin secretion in isolated mice islets, and its insulinotropic effect was exerted at high glucose concentrations distinctly different from glibenclamide. Myricetin-induced insulin secretion was significantly inhibited using the diazoxide. Furthermore, myricetin amplified glucose-induced insulin secretion in depolarized and glibenclamide-treated islets. Myricetin showed an additive effect with forskolin- and IBMX-induced insulin secretion. Interestingly, H89, a PKA inhibitor, and MAY0132, an Epac-2 inhibitor, significantly inhibited myricetin-induced insulin secretion. The in silico molecular docking studies further validated these in vitro findings in isolated pancreatic islets. Conclusions: Myricetin, a potential natural insulin secretagogue, amplifies glucose-induced insulin secretion via the cAMP-PKA-Epac-2 signaling pathway. Full article

Microalgae represent promising biotechnological platforms for bioactive compound production with pharmaceutical applications. This study investigated the phytochemical composition and biological activities of lipid extracts from three Chlorella species to evaluate their potential as antioxidant and antidiabetic sources. Lipid extraction using chloroform–methanol (2:1) followed by GC–MS analysis revealed distinct compound distributions: 29 compounds in C. ellipsoidea, 33 in C. sorokiniana, and 19 in C. vulgaris. Major bioactive compounds included 2-hexanol, 1,3,6-heptatriene, 4-(2,3-dimethyl-2-cyclopenten-1-yl)-4-methylpentanal, n-hexadecanoic acid, and octadecanoic acid. Biological activity screening encompassed antioxidant assessment through DPPH• and •NO radical scavenging assays and FRAP analysis, while antidiabetic potential was evaluated using α-glucosidase and α-amylase inhibition assays. C. sorokiniana exhibited superior bioactivity with the highest antioxidant capacity (DPPH• IC₅₀ = 329.03 ± 4.30 µg/mL; •NO IC₅₀ = 435.53 ± 10.20 µg/mL; FRAP = 94.74 ± 5.72 mg TE/g) and strongest enzyme inhibition (α-glucosidase IC₅₀ = 752.75 ± 57.95 µg/mL; α-amylase IC₅₀ = 3458.50 ± 104.01 µg/mL). This is the first report on C. sorokiniana strain KU.B2′s biological properties and phytochemical profile. These findings establish C. sorokiniana as a valuable biotechnological platform for pharmaceutical bioactive compound development. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by impaired glucose regulation. This study evaluated the antioxidant and antidiabetic potential of aqueous extracts from four plant species from the southern Algarve: Aristolochia baetica, Chelidonium majus, Dittrichia viscosa, and Lavandula viridis, using non-cellular in vitro assays. HPLC/PDA was used to identify active compounds. Antioxidant activity was assessed by using TAA, FRAP, RP, and DPPH assays; antidiabetic potential through α-glucosidase and α-amylase inhibition; and wound healing relevance through elastase, collagenase, and lipoxygenase inhibition. D. viscosa showed the highest antioxidant activity (FRAP: 1132.99 ± 19.54 mg TE/g dw; DPPH IC₅₀ = 25.85 ± 0.75 μg/mL) and total phenolic/flavonoid content, with a diverse profile including caffeic and chlorogenic acids, isoquercetin, and quercetin. It also exhibited potent α-glucosidase inhibition (IC₅₀ = 0.61 ± 0.06 mg/mL), outperforming acarbose. L. viridis had the highest total phenolic content (39.04 mg/g), while A. baetica demonstrated the strongest anti-elastase, anti-collagenase, and lipoxygenase activity, suggesting wound-healing potential. C. majus showed the weakest effects. A strong correlation was observed between phenolic content and antioxidant/antidiabetic activity. These findings support further in vivo studies on D. viscosa and A. baetica for potential use in T2DM management and diabetic wound healing. Full article

Type 2 diabetes mellitus remains a critical global health challenge, driving the pursuit of novel therapeutic strategies. This study investigated the anti-diabetic efficacy of the peptide 1CBR, derived from sodium caseinate hydrolysate, administered orally at 25 mg/kg/day to db/db mice over a 4-week period. Glucose tolerance was evaluated via oral glucose tolerance tests (OGTT), while plasma dipeptidyl peptidase-IV (DPP-IV) activity, glucagon-like peptide-1 (GLP-1), and insulin concentrations were quantified using enzyme-linked immunosorbent assays (ELISA). Two bioactive peptides, GPFPLPD and APDSGNFR, were isolated and characterized, exhibiting half-maximal inhibitory concentrations (IC₅₀) of 99.12 µM and 73.07 µM for DPP-IV inhibition, respectively, and both significantly stimulated GLP-1 secretion in enteroendocrine cells in vitro. Pharmacokinetic analysis in Sprague–Dawley rats demonstrated oral bioavailability of 11.28% and 19.12% for these peptides, surpassing typical expectations for peptide-based agents. Collectively, these results provide compelling evidence that 1CBR-derived peptides exert glucose-lowering effects through the dual mechanisms of DPP-IV inhibition and GLP-1 stimulation, combined with favorable oral absorption profiles. These findings underscore the potential of 1CBR peptides as promising candidates for development into nutraceuticals or pharmaceutical agents for diabetes management. Full article